Individuals addicted to stimulant drugs like cocaine are at high risk for engaging in sexual behaviors that contribute to the acquisition of HIV and, once infected, to the forward transmission of HIV to others. HIV-related decision making, like most real-world decisions, involves the valuation of potential gains and losses in the context of uncertain outcomes. Cocaine dependence and HIV infection can each disrupt brain circuits that regulate executive functions involved in decision making. We postulate that these neural changes affect the processing of reward evaluation and outcome uncertainty and contribute to sexual risk behavior. Our preliminary work suggests that cocaine dependence increases loss aversion (i.e., overweighting of potential losses relative to potential gains), and that HIV infecton is associated with greater risk taking propensity among persons with cocaine dependence. Moreover, loss aversion is positively correlated with sexual risk behavior, suggesting that basic decision making processes may be predictive of more complex real-world behavior. The proposed research builds upon our prior work by combining functional neuroimaging, behavioral risk assessment, and computational modeling to: (1) isolate the effects of cocaine dependence and HIV infection on decision making processes, specifically loss aversion and ambiguity tolerance, and (2) examine the relationship between these decision making processes and sexual risk behavior. Using a case-control design, we will examine behavioral choice and brain activity during monetary gambles that vary independently on the value of gains and losses and the certainty of outcomes. The sample will include 80 adults who differ on cocaine and HIV status, comprising four distinct groups (20/group). Our multidisciplinary team, with expertise in clinical psychology, cognitive neuroscience, behavioral neuroeconomics, and MR physics, has extensive experience conducting patient-oriented research on HIV risk behavior in persons with drug dependence and is uniquely poised to successfully implement this innovative and clinically important project. Results of this R21 proposal will provide unique insights into the mechanisms underlying HIV-related decision making, providing support for a subsequent R01 application to further investigate how HIV disease progression may affect neural processes that contribute to risky decision making among cocaine users. This research has strong potential for translation to clinical practice, informing the development of novel interventions to more effectively reduce risk behavior by directly targeting underlying neurocognitive deficits, with the ultimate goal of reducing HIV- related morbidity and mortality in persons with drug use disorders.